A Prospective Multicenter Phase 2 Study of the Chemotherapy-Free Combination of the Intravenous Phosphatidylinositol-3-Kinase (PI3K) Inhibitor Copanlisib in Combination With Obinutuzumab in Patients With Previously Untreated Follicular Lymphoma (FL) and a High Tumor Burden
Alternative-C
2 other identifiers
interventional
98
1 country
40
Brief Summary
The Alternative-C Trial is a prospective, multicenter Phase 2 Study to evaluate the efficacy of the chemotherapy-free combination of copanlisib and obinutuzumab in patients with previously untreated follicular lymphoma (FL) and a high tumor burden. Additionally, the combination should be evaluated in terms of secondary efficacy endpoints, treatment compliance, safety and patient-reported symptoms. The study Population includes Patients \> 18 years of age with histologically confirmed follicular lymphoma grade 1, 2 or 3A with Ann Arbor Stage III/IV or stage II not suitable for radiotherapy and in need of therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Oct 2020
Longer than P75 for phase_2
40 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 19, 2020
CompletedFirst Submitted
Initial submission to the registry
January 27, 2022
CompletedFirst Posted
Study publicly available on registry
May 24, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 16, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
May 19, 2026
CompletedMarch 12, 2024
March 1, 2024
2.9 years
January 27, 2022
March 7, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
One-year progression-free survival (PFS) probability from study registration
The rate of patients achieving a progression free survival of more than one year after registration (one-year PFS rate) will serve as early readout for efficacy.
1 year
Secondary Outcomes (14)
Complete remission (CR) rates and overall response (CR or partial remission, PR) rates
at end of induction (month 6), at end of consolidation (month 12), and at end of maintenance (month 30)
Progression free survival from registration
continuous observation up to 78 months
Duration of response
from end of induction to progression or death assessed up to 72 months
Cumulative incidence of progression
from registration to end of study assessed up to 78 months
Failure-free survival
from start of therapy assessed up to 78 months
- +9 more secondary outcomes
Study Arms (1)
Copanlisib + Obinutuzumab
EXPERIMENTALInterventions
Induction therapy will comprise 6 cycles of copanlisib, administered by intravenous Infusion at a dose of 60 mg on day 1,8,15 of cycles 1-6 to be given every 28 days. Consolidation therapy will comprise another 24 weeks of copanlisib in patients with clinical Remission 28 days after the last induction cycle. It will be administered by intravenous Infusion at a dose of 60 mg on days 1 and 15 of cycles 7 - 12 to be given every 28 days. Maintenance therapy will comprise another 72 weeks of copanlisib in patients with clinical remissions 28 days after the last consolidation cycle.
Induction therapy will comprise 6 cycles of obinutuzumab, administered by intravenous infusion at a dose of 1000 mg on days 1,8, 15 of cycle 1 and on day 1 of cycles 2 - 6 to be given every 28 days. Consolidation therapy will comprise of another 24 weeks of obinutuzumab in patients with clinical remission 28 days after the last induction cycle. Obinutuzumab will be applied at a dose of 1000 mg by intravenous infusion every 8 weeks. Maintenance therapy will comprise another 72 weeks in patients with clinical remission 28 days after the last consolidation cycle. Obinutuzumab will be applied at a dose of 1000 mg by intravenous infusion every 8 weeks.
Eligibility Criteria
You may qualify if:
- Subjects will only be included in the study, if they meet all of the following criteria:
- Histologically confirmed follicular lymphoma grade 1, 2 or 3A with a biopsy performed within 12 months before study entry and with material available for central review and complementary scientific analyses
- Ann Arbor stage III/IV, or stage II not suitable for radiotherapy, or stage II bulky disease
- Age ≥ 18 years
- No prior lymphoma therapy
- Need for start of therapy as defined by at least one of the following criteria:
- bulky disease at study entry according to the GELF criteria (nodal or extranodal mass \> 7 cm in its greatest diameter)
- B symptoms (fever, drenching night sweats, or unintentional weight loss of \> 10% of normal body weight over a period of 6 months or less)
- hematopoietic insufficiency (granulocytopenia \< 1500/µl, Hb \< 10 g/dl, thrombocytopenia \< 100000/µl)
- compressive syndrome or high risk for compression syndrome
- pleural/peritoneal effusion
- symptomatic extranodal manifestations
- At least one bi-dimensionally measurable lesion (\> 2 cm in its largest dimension by CT scan or MRI)
- Performance status ≤ 2 on the ECOG scale
- Adequate hematologic function (unless abnormalities are related to NHL), defined as follows:
- +6 more criteria
You may not qualify if:
- Subjects will not be included in the study if any of the following criteria apply:
- Transformation to high-grade lymphoma (secondary to "low grade" FL)
- Grade 3B follicular lymphoma
- Presence or history of CNS disease (either CNS lymphoma or leptomeningeal lymphoma)
- Known hypersensitivity to any of the study drugs
- Known sensitivity to murine products
- Patients with HbA1c \> 8.5 % at Screening
- Uncontrolled arterial hypertension despite optimal medical management (per investigator's assessment)
- Regular use of corticosteroids during the last 4 weeks, unless administered at a dose equivalent to \< 20 mg/day prednisone or administered as prephase treatment according to study protocol (see section 7.2 of study protocol)
- Concomitant use of strong CYP3A4 inhibitors and/or inducers
- Prior or concomitant malignancies except:
- non-melanoma skin cancer or adequately treated in carcinoma in situ of the cervix
- other malignant diseases not specified above which have been curatively treated by surgery alone and from which subject is disease-free for ≥ 5 years without further treatment
- Serious disease interfering with a regular therapy according to the study protocol:
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
- +18 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Ludwig-Maximilians - University of Munichlead
- Roche Pharma AGcollaborator
- Bayercollaborator
Study Sites (40)
LMU Klinikum
München, Bavaria, 81377, Germany
Gesundheitszentrum St. Marien GmbH
Amberg, 92224, Germany
HELIOS Klinikum Bad Saarow
Bad Saarow, 15526, Germany
Vivantes Netzwerk für Gesundheit GmbH - Vivantes Klinikum am Urban
Berlin, 10967, Germany
Charité Campus Benjamin Franklin
Berlin, 12200, Germany
Universitätsklinikum Bonn
Bonn, 53127, Germany
Klinikum Chemnitz gGmbH
Chemnitz, 09113, Germany
Carl-Thiem-Klinikum Cottbus gGmbH
Cottbus, 03048, Germany
Cancer Center Dachau
Dachau, 85221, Germany
Städtisches Klinikum Dessau
Dessau, 06847, Germany
Gemeinschaftspraxis Dr. med. J. Mohm und Dr. med. G. Prange-Krex
Dresden, 01307, Germany
Marien Hospital Düsseldorf
Düsseldorf, 40479, Germany
Universitätsklinikum Essen
Essen, 45147, Germany
Centrum für Hämatologie und Onkologie Bethanien
Frankfurt am Main, 60389, Germany
Universitätsklinikum Freiburg
Freiburg im Breisgau, 79106, Germany
Universitätsklinikum Heidelberg
Heidelberg, 69120, Germany
Universitätsklinikum Jena
Jena, 07747, Germany
Klinikum Kassel
Kassel, 34125, Germany
Universitätsklinikum Schleswig-Holstein
Kiel, 24105, Germany
Praxis für Hämatologie und Onkologie
Koblenz, 56068, Germany
Klinikum der Stadt Ludwigshafen gGmbH
Ludwigshafen, 67063, Germany
Schwerpunktpraxis für Hämatologie und Onkologie
Magdeburg, 39104, Germany
Universitätsklinikum Magdeburg A.ö.R.
Magdeburg, 39120, Germany
Universitätsklinik Mannheim
Mannheim, 68167, Germany
Kliniken Maria Hilf GmbH, Krankenhaus St. Franziskus
Mönchengladbach, 41063, Germany
Stauferklinikum Schwäbisch Gmünd
Mutlangen, 73557, Germany
Klinikum rechts der Isar der TU München
München, 81675, Germany
Gemeinschaftspraxis für Hämatologie und Onkologie
Münster, 48149, Germany
Universitätsklinikum Münster
Münster, 48149, Germany
Friedrich Ebert Krankenhaus
Neumünster, 24534, Germany
Rheinland Klinikum, Lukaskrankenhaus Neuss
Neuss, 41464, Germany
Brüderkrankenhaus St. Josef Paderborn
Paderborn, 33098, Germany
Universitätsmedizin Rostock
Rostock, 18057, Germany
Klinikum Südstadt Rostock
Rostock, 18059, Germany
Gemeinschaftspraxis Dr. med. G.A. Jacobs
Saarbrücken, 66111, Germany
Klinikum Mutterhaus der Borromäerinnen gGmbH
Trier, 54290, Germany
Universitätsklinikum Tübingen
Tübingen, 72076, Germany
Universitätsklinikum Ulm
Ulm, 89081, Germany
Petrus Kankenhaus
Wuppertal, 42283, Germany
Hämatologisch-Onkologische Schwerpunktpraxis
Würzburg, 97080, Germany
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Christian Schmidt, Dr.
LMU Klinikum, Medical department III
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Dr. Christian Schmidt
Study Record Dates
First Submitted
January 27, 2022
First Posted
May 24, 2022
Study Start
October 19, 2020
Primary Completion
September 16, 2023
Study Completion
May 19, 2026
Last Updated
March 12, 2024
Record last verified: 2024-03
Data Sharing
- IPD Sharing
- Will not share